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Background: Status epilepticus (SE) is a common neurological emergency with high mortality, and is often the first manifestation of a seizure disorder. When faced with a patient in SE (or severe cluster seizures) our priority should always be to stop the seizure activity; however, this should not distract us from assessing our seizuring patient as a whole. Neglecting to do so could lead to severe complications and could dramatically affect the patient's short‐term outcome. Management of dogs in SE requires a swift, coordinated response from all members of the veterinary team to improve chances of survival. Aim of the article: This article aims to provide a step‐by‐step guide for the management of dogs in SE with a focus on strategies to best monitor, stabilise and treat this neurological emergency. [ABSTRACT FROM AUTHOR]

Lead poisoning from feeding on carcasses shot with lead‐based ammunition is a well‐known threat to wildlife. Thus, nonlead (e.g., copper‐based) ammunition is promoted as a safe alternative. We present a unique situation of a male California condor (Gymnogyps californianus) discovered with both a lead fragment and a copper bullet in his digestive tract simultaneously. We show that ingestion of a copper bullet did not result in elevated blood copper concentrations, while ingestion of a lead fragment contributed to lead toxicity. Our findings can inform nonlead ammunition outreach efforts by demonstrating that ingestion of a copper‐based bullet did not result in the poisoning of a California condor. [ABSTRACT FROM AUTHOR]

Background: This retrospective chart review sought to determine whether the introduction of a safe person handling and mobility (SPHM) program resulted in changes to the frequency, severity, cost, or profile of staff injuries incurred during person handling (PH) tasks at long‐term care settings for persons with complex conditions. Methods: This study analyzed the SPHM program implementation at an organization providing long‐term residential, day habilitation, and special education services for persons with complex conditions. Data covered two 4‐year periods before and after implementation. Analyses compared the frequency, severity, and cost of staff PH injuries, as well as of the affected body area, staff role, level of treatment, and the incurred costs of Workers' Compensation (WC) claims. Results: There were substantive decreases in the total number of staff PH injuries and WC claims. Staff PH injuries affecting the trunk, the area most associated with PH injuries, decreased the most, followed by the upper extremities. Reductions were concentrated among direct care employees and their supervisors, job titles where PH exposures are most commonly seen. The proportion of staff injuries requiring medical treatment decreased significantly, as did injury severity. The number of lost workdays decreased by 94.6%. Incurred WC costs decreased by 91.1%. The proportion of WC claims associated with lost time decreased significantly. Conclusions: Substantive reductions in the frequency, severity, and incurred WC cost of staff PH injuries followed implementation of the SPHM program. Likewise, proportional changes were identified among the programs where cases occurred, the need for medical treatment, and WC cost type. [ABSTRACT FROM AUTHOR]

Objectives: Medical cannabis formulations with cannabidiol (CBD) and delta‐9‐tetrahydrocannabinol (THC) are widely used to treat epilepsy. We studied the safety and efficacy of two formulations. Methods: We prospectively observed 29 subjects (12 to 46 years old) with treatment‐resistant epilepsies (11 Lennox–Gastaut syndrome; 15 with focal or multifocal epilepsy; three generalized epilepsy) were treated with medical cannabis (1THC:20CBD and/or 1THC:50CBD; maximum of 6 mg THC/day) for ≥24 weeks. The primary outcome was change in convulsive seizure frequency from the pre‐treatment baseline to the stable optimal dose phase. Results: There were no significant differences during treatment on stable maximal doses for convulsive seizure frequency, seizure duration, postictal duration, or use of rescue medications compared to baseline. No benefits were seen for behavioral disorders or sleep duration; there was a trend for more frequent bowel movements compared to baseline. Ten adverse events occurred in 6/29 patients, all were transient and most unrelated to study medication. No serious adverse events were related to study medication. Interpretation: Our prospective observational study of two high‐CBD/low‐THC formulations found no evidence of efficacy in reducing seizures, seizure duration, postictal duration, or rescue medication use. Behavioral disorders or sleep duration was unchanged. Study medication was generally well tolerated. The doses of CBD used were lower than prior studies. Randomized trials with larger cohorts are needed, but we found no evidence of efficacy for two CBD:THC products in treating epilepsy, sleep, or behavior in our population. [ABSTRACT FROM AUTHOR]

Bacteria employ noncoding RNA molecules for a wide range of biological processes, including scaffolding large molecular complexes, catalyzing chemical reactions, defending against phages, and controlling gene expression. Secondary structures, binding partners, and molecular mechanisms have been determined for numerous small noncoding RNAs (sRNAs) in model aerobic bacteria. However, technical hurdles have largely prevented analogous analyses in the anaerobic gut microbiota. While experimental techniques are being developed to investigate the sRNAs of gut commensals, computational tools and comparative genomics can provide immediate functional insight. Here, using Bacteroides thetaiotaomicron as a representative microbiota member, we illustrate how comparative genomics improves our understanding of RNA biology in an understudied gut bacterium. We investigate putative RNA‐binding proteins and predict a Bacteroides cold‐shock protein homolog to have an RNA‐related function. We apply an in silico protocol incorporating both sequence and structural analysis to determine the consensus structures and conservation of nine Bacteroides noncoding RNA families. Using structure probing, we validate and refine these predictions and deposit them in the Rfam database. Through synteny analyses, we illustrate how genomic coconservation can serve as a predictor of sRNA function. Altogether, this work showcases the power of RNA informatics for investigating the RNA biology of anaerobic microbiota members. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that presents with recurrent inflammatory nodules and draining tunnels in the skin. Most HS studies have focused on Western populations, and the understanding of how HS characteristics differ in specific Asian ethnicities is poor. We conducted the first systematic review and meta‐analysis to characterize HS patients from East and Southeast Asia. PubMed, Embase, and Ovid MEDLINE databases were searched from inception to June 12, 2020. English‐language case‐series, cross‐sectional, observational, and randomized controlled trial studies investigating HS in East and Southeast Asian populations were screened by titles, abstracts, and articles in duplicate. Of 136 citations, 10 studies were included in the meta‐analysis. Data on gender distribution, lesion distribution in the axilla and gluteal regions, and family history were extracted in duplicate. A random effects model was used for the meta‐analysis. A total of 30,125 HS patients were included in the analysis. Most patients were male (66%, 95% CI = 60–72%). About half of Asian patients with HS develop lesions in the axilla (52%, 95% CI = 33–72%) and the buttocks (48%, 95% CI = 38–57%). Only a small subset had positive family history of HS (5%, 95% CI = 2–8%). We report an up‐to‐date characterization of HS in East and Southeast Asian populations and highlight differences in their Western counterparts. These results will hopefully improve understanding for how HS may manifest, lead to more personalized treatments for Asian patients with HS, and usher in a proper patient‐centered approach to treating the disease. [ABSTRACT FROM AUTHOR]

Aim: Many species face large‐scale range contractions and predicted distributional shifts in response to climate change, shifting forest characteristics and anthropogenic disturbances. Canada lynx (Lynx canadensis) are listed as threatened under the U.S. Endangered Species Act and were recently recommended for delisting. Predicted climate‐driven losses in habitat quality and quantity may negatively affect the north‐eastern Minnesota lynx population, one of the six remaining resident populations in the contiguous United States. We develop a large‐scale monitoring protocol and dynamic occupancy modelling framework to identify multi‐year core‐use areas and track spatiotemporal occurrence at the southern periphery of the species range. Location: North‐eastern Minnesota lynx geographic unit, Superior National Forest and designated critical habitat, Minnesota, USA. Methods: Spatially and temporally replicated snow track surveys were used to collect lynx detection/non‐detection data across five winters (2014–15 to 2018–19) covering >17,000 km within the 22,100 km2 study area. We used a dynamic occupancy model to evaluate lynx occupancy, persistence, colonization and habitat covariates affecting these processes. Results: Lynx occupancy probabilities displayed high spatial and temporal variability, with grid cell‐specific probabilities ranging from 0.0 in periphery regions to consistently near 1.0 in multi‐year core‐use areas, indicating low turnover rates in those areas. Lynx colonization and persistence increased in areas with more evergreen forest and greater average snowfall, while forest characteristics (3–5 and 10–30 m vegetation density) had mixed relationships with occupancy dynamics. We identified 55 grid cells classified as multi‐year core‐use areas across relatively contiguous regions of high average snowfall and per cent conifer forest. Main conclusions: Our study demonstrates a landscape‐scale multi‐year monitoring programme assessing the effects of habitat characteristics and anthropogenic factors on species distributional changes and landscape‐level occupancy dynamics. Our framework incorporating landscape‐scale resource selection, core‐use area concepts and dynamic occupancy models provides a flexible approach to identify population‐level mechanisms driving species persistence and key areas for conservation protection. [ABSTRACT FROM AUTHOR]

A transmission geometry optical configuration allows for smaller laser spot size to facilitate high-resolution matrix-assisted laser/desorption ionization (MALDI) mass spectrometry. This increase in spatial resolution (ie, smaller laser spot size) is often associated with a decrease in analyte signal. MALDI-2 is a post-ionization technique, which irradiates ions and neutrals generated in the initial MALDI plume with a second orthogonal laser pulse, and has been shown to improve sensitivity. Herein, we have modified a commercial Orbitrap mass spectrometer to incorporate a transmission geometry MALDI source with MALDI-2 capabilities to improve sensitivity at higher spatial resolutions. [ABSTRACT FROM AUTHOR]

Rationale: Liquid extraction surface analysis (LESA) can be used to generate spatially directed protein identifications in an imaging mass spectrometry (IMS) workflow. This approach involves the use of robotic micro‐extractions coupled to online liquid chromatography (LC). We have characterized the extraction efficiency of this method as well as its ability to identify proteins from a matrix assisted laser/desorption ionization (MALDI) IMS experiment. Methods: Proteins and peptides were extracted from transverse sections of a rat brain and sagittal sections of a mouse pup using liquid surface extractions. Extracts were either analyzed by online LC coupled to a high mass resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometer or collected offline and analyzed by traditional LC/MS methods. Identifications were made using both top‐down and bottom‐up methodologies. MALDI images were acquired on a 15T FTICR mass spectrometer at 125 μm spatial resolution. Results: Robotic liquid surface extractions are reproducible across various tissue types, providing significantly improved spatial resolution, with respect to extractions, while still allowing for a robust number of protein identifications. A single 2‐μL extract can provide identification of over 14,000 peptides with little sample preparation, increasing throughput for spatially targeted workflows. Surface extractions from tissue were coupled directly to LC to gather spatially relevant proteomics data. Conclusions: Robotic liquid surface extractions can be used to interrogate discrete regions of tissue to provide protein identifications with high throughput, accuracy, and robustness. The direct coupling of tissue surface extractions and LC offers a new and effective approach to provide spatial proteomics data in an imaging experiment. [ABSTRACT FROM AUTHOR]

Small molecules were developed to attenuate proinflammatory cytokines resulting from activation of MyD88-mediated toll-like receptor ( TLR) signaling by Francisella tularensis. Fifty-three tripeptide derivatives were synthesized to mimic a key BB-loop region involved in toll-like/interleukin-1 receptor recognition ( TIR) domain interactions. Compounds were tested for inhibition of TNF-α, IFN-γ, IL-6, and IL-1β in human peripheral blood mononuclear cells ( PBMCs) and primary human bronchial epithelial cells exposed to LPS extracts from F. tularensis. From 53 compounds synthesized and tested, ten compounds were identified as effective inhibitors of F. tularensis LPS-induced cytokines. Compound stability testing in the presence of human liver microsomes and human serum resulted in the identification of tripeptide derivative 7 that was a potent, stable, and drug-like small molecule. Target corroboration using a cell-based reporter assay and competition experiments with MyD88 TIR domain protein supported that the effect of 7 was through MyD88 TIR domain interactions. Compound 7 also attenuated proinflammatory cytokines in human peripheral blood mononuclear cells and bronchial epithelial cells challenged with a live vaccine strain of F. tularensis at a multiplicity of infection of 1:5. Small molecules that target TIR domain interactions in MyD88-dependent TLR signaling represent a promising strategy toward host-directed adjunctive therapeutics for inflammation associated with biothreat agent-induced sepsis. [ABSTRACT FROM AUTHOR]

Optimal policy recommendations from natural resource management models can involve fast-changing management interventions. Actual policies often change more gradually, potentially reflecting costs associated with policy adjustment. We examine how including policy adjustment costs changes policy recommendations in models of fishery management. Specifically, we examine cases where policy adjustment costs increase at an increasing rate with the rate of change of fishing effort levels. We examine how accounting for these costs changes optimal management strategies in static and time-varying environments. Increasing policy adjustment costs results in optimal approach paths to stationary optimal solutions that are more gradual but that rely on oscillatory convergence. In time-varying environments, including policy adjustment costs smoothes optimal management recommendations, resulting in decreased variation in effort levels on the stationary part of the optimal solution, but increased variation in optimal stock sizes. We conclude that accounting for policy adjustment costs in this way leads to management recommendations that in some ways would be simpler for managers to implement (more gradual approach paths), but in other ways more challenging (oscillatory convergence) and that can affect where environmental variability is expressed in model predictions (stock sizes versus effort levels) while not suppressing this variability altogether. [ABSTRACT FROM AUTHOR]

The rational design of a flexible molecular box, oAzoBox4+, incoporating both photochromic and supramolecular recognition motifs is described. We exploit the E↔ Z photoisomerization properties of azobenzenes to alter the shape of the cavity of the macrocycle upon absorption of light. Imidazolium motifs are used as hydrogen-bonding donor components, allowing for sequestration of small molecule guests in acetonitrile. Upon E→ Z photoisomerization of oAzoBox4+ the guest is expelled from the macrocyclic cavity. [ABSTRACT FROM AUTHOR]

Dilation or aneurysm of the ascending aorta can progress to acute aortic dissection (Thoracic Aortic Aneurysms and Aortic Dissections, TAAD). Mutations in genes encoding TGF-β-related proteins ( TGFBR1, TGFBR2, FBN1, and SMAD3) cause syndromic and inherited TAAD. SMAD4 mutations are associated with juvenile polyposis syndrome (JPS) and a combined JPS-hereditary hemorrhagic telangiectasia (HHT) known as JPS-HHT. A family with JPS-HHT was reported to have aortic root dilation and mitral valve abnormalities. We report on two patients with JPS-HHT with SMAD4 mutations associated with thoracic aortic disease. The first patient, an 11-year-old boy without Marfan syndrome features, had JPS and an apparently de novo SMAD4 mutation (c.1340_1367dup28). Echocardiography showed mild dilation of the aortic annulus and aortic root, and mild dilation of the sinotubular junction and ascending aorta. Computed tomography confirmed aortic dilation and showed small pulmonary arteriovenous malformations (PAVM). The second patient, a 34-year-old woman with colonic polyposis, HHT, and features of Marfan syndrome, had a SMAD4 mutation (c.1245_1248delCAGA). Echocardiography showed mild aortic root dilation. She also had PAVM and hepatic focal nodular hyperplasia. Her family history was significant for polyposis, HHT, thoracic aortic aneurysm, and dissection and skeletal features of Marfan syndrome in her father. These two cases confirm the association of thoracic aortic disease with JPS-HHT resulting from SMAD4 mutations. We propose that the thoracic aorta should be screened in patients with SMAD4 mutations to prevent untimely death from dissection. This report also confirms that SMAD4 mutations predispose to TAAD. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Use of RNA later (Ambion, Inc.) solution to preserve whole organisms for nucleic acid analysis is gaining popularity, in part because it effectively preserves both RNA and DNA without the need for freezing the organism. Similar preservatives have been shown to cause short-term changes in animal length, and such changes must be accounted for as analyses progress. We examined the rates and degrees of shrinkage for freshwater amphipods spp. and larval yellow perch after preservation in RNA later solution in comparison with more common preservatives. We found that after 2 months of preservation, Diporeia shrank by 3% in RNA later versus gaining length by 5% in diluted ethanol and by 1% in diluted formaldehyde. After 5.5 months of preservation, larval yellow perch lengths decreased by 23% in RNA later, 10% in diluted ethanol, 12% in diluted formaldehyde, and 19% when frozen in water. Overall length reduction for Diporeia and larval yellow perch was significantly greater in RNA later than in ethanol or formalin. Since accurate measures of length are necessary for many nucleic acid analyses, researchers utilizing RNA later solution should attempt to measure organisms while they are alive or should develop preservation-specific correction functions to overcome biases associated with shrinkage. [ABSTRACT FROM AUTHOR]

Background: Previously identified atherosclerotic genetic factors have been studied mostly in case-control studies and in nonuniform ethnic populations, whereas data on the cumulative contribution of genetic factors to an earlier onset of a first myocardial infarction (MI) are limited. We hypothesized that several genetic atherosclerotic single nucleotide polymorphisms (SNPs) may exert an additive effect on the earlier occurrence of coronary atherothrombotic disease after adjustment for clinical factors. Methods: Eighteen atherosclerotic high-risk SNPs were selected based upon meta-analyses of 614 published reports, and were incorporated into a carriership model. Multivariate regression analysis was used to identify the independent contribution of selected genotypes to the age at onset of a first MI in a cohort of 814 white (n = 622) and nonwhite (n = 192) patients enrolled in the Thrombogenic Factors and Coronary Events Study. Results: The analysis demonstrated that selected genotypes were significantly associated with an earlier occurrence of a first MI among white patients (an average of 0.6 year reduction per carried genotype; P = 0.027), whereas the contribution of genotypes to MI onset among nonwhite patients was not significant (an average of 0.7 year increase per carried genotype; P = 0.16), with a significant ethnic × genotype interaction effect (P = 0.02). Conclusions: Our findings suggest that currently identified atherosclerotic genetic factors confer an independent additive contribution to the earlier onset of coronary atherothrombotic disease among white patients. The lack of a significant association between these genotypes and outcome in other ethnic groups suggests that cardiovascular genetic risk should be studied directly in these populations. [ABSTRACT FROM AUTHOR]

The nuclear proteins TAL1 (T-cell acute leukaemia protein 1) and LMO2 (LIM-only protein 2) have critical roles in haematopoietic development, but are also often aberrantly activated in T-cell acute lymphoblastic leukaemia. TAL1 and LMO2 operate within multifactorial protein-DNA complexes that regulate gene expression in the developing blood cell. TAL1 is a tissue-specific basic helix-loop-helix (bHLH) protein that binds bHLH domains of ubiquitous E-proteins, (E12 and E47), to bind E-box (CANNTG) DNA motifs. TAL1bHLH also interacts specifically with the LIM domains of LMO2, which in turn bind Ldb1 (LIM-domain binding protein 1). Here we used biophysical methods to characterize the assembly of a five-component complex containing TAL1, LMO2, Ldb1, E12, and DNA. The bHLH domains of TAL1 and E12 alone primarily formed helical homodimers, but together preferentially formed heterodimers, to which LMO2 bound with high affinity ( KA ∼ 108 M−1). The resulting TAL1/E12/LMO2 complex formed in the presence or absence of DNA, but the different complexes preferentially bound different Ebox-sequences. Our data provide biophysical evidence for a mechanism, by which LMO2 and TAL1 both regulate transcription in normal blood cell development, and synergistically disrupt E2A function in T-cells to promote the onset of leukaemia. Proteins 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking and the common B1 allele of the TaqIB polymorphism have both been reported to be associated with increased cholesteryl ester transfer protein (CETP) activity and altered lipoprotein levels. Thus, it is possible that the combined presence of these two respective environmental and genetic factors may enhance cardiovascular risk. We hypothesized that susceptibility to early onset myocardial infarction (MI) among cigarette smokers may be related to the presence of TaqIB polymorphism in the CETP gene.Methods: The age at onset of a first MI among current (n = 199), past (n = 345), and never (n = 270) smokers was related to the presence of the TaqIB1 and B2 alleles in a cohort of 814 first MI patients.Results: Multivariate regression analysis demonstrated that cigarette smoking was associated with a significant increase in the risk for early onset MI only among carriers of the TaqIB1 allele: current smokers with the B1B1 and B1B2 genotypes displayed a respective 9.4 (P < 0.001) and 8.4 (P < 0.001) year reduction in the age at onset of a first MI compared with never smokers, and past smokers with these genotypes exhibited a respective 3.8 (P = 0.003) and 3.7 (P = 0.01) year reduction. By contrast, current and past smoking was not associated with a significant increase in the risk for early onset MI among B2B2 homozygotes (3.0 [P = 0.28] and 0.2 [P = 0.93] year reduction, respectively). The smoking x genotype interaction was statistically significant (P = 0.04).Conclusions: The current findings suggest that genetic factors may modify susceptibility to early onset MI among cigarette smokers. [ABSTRACT FROM AUTHOR]

The beta-binomial distribution is used to provide estimates of the probability of detecting a rare species, the smallest proportion cover detectable with a stated confidence for a survey, and is a method for estimating the sample size required to detect a species with a stated presence at a stated level of confidence for independent clusters of binary data. The equations, while general were derived in the context of marine benthic video transects and are useful for evaluating a wide range of existing surveys or designing new surveys. Application of the equations is demonstrated for a data set collected from three marine surveys on the Great Barrier Reef in Australia. [ABSTRACT FROM AUTHOR]

Nonparametric methods can be used to analyze failure times and estimate probability distributions for failures of systems due to successful attacks on confidentiality, integrity, and availability in information security. However, such methods do not take full advantage of supplemental information regarding the configurations of systems in an information infrastructure that is usually also available. One approach, which does take advantage of such information, views the risks of systems failing from various causes as competing risks and determines the correlation coefficients of different treatments to system longevity. Since the times and causes of failure in such studies are usually uncorrelated, the hazards associated with each risk are proportional. By correlating system survival times to the use of specific design enhancements and security countermeasures, as well as to system exposure based on choice of operational functionality, guidance can be obtained for making investments in information security. [ABSTRACT FROM AUTHOR]

Studies the breeding biology of wood ducks in Southern Illinois. Details on the study area; Methodology used; Information on the nest sites and productivity.

Stem cell factor (SCF) is hypothesized to play a critical role in the migration of melanocytes during embryogenesis because mutations in either the SCF gene, or its ligand, c-kit, result in defects in coat pigmentation in mice and in skin pigmentation in humans. In this report we directly show that SCF alters the adhesion and migration of human melanocytes to extracellular matrix (ECM) ligands and regulates integrin expression at the protein level. SCF decreased adhesion of neonatal and fetal cells to collagen IV, and increased attachment of fetal cells to laminin. Attachment of fetal cells to fibronectin was decreased, but was unchanged in neonatal cells. Flow cytometry analysis of neonatal melanocytes showed that SCF down-regulated the expression of the α2 receptor, and up-regulated the expression of the α3, α5 and β1 integrin receptors. SCF down-regulated expression of α2, α5 and β1 integrins by fetal melanocytes, and up-regulated expression of the αv and α3 integrin receptors. Analysis of melanocyte migration using time-lapse videomicroscopy showed that SCF significantly increased migration of neonatal, but not fetal, melanocytes on fibronectin (FN). We conclude that SCF regulates integrin expression at the protein level and that SCF has pleiotropic effects on melanocyte attachment and migration on ECM ligands. We suggest that this may be one mechanism by which SCF regulates melanocyte migration during development of the skin. [ABSTRACT FROM AUTHOR]

The cover page of the journal "Angewandte Chemie" is presented.

Lichtgetriebene Konformationsänderungen in einem makrocyclischen Wirt ermöglichen die kontrollierte Verkapselung und Freisetzung von Gastspezies. J. del Barrio, O. A. Scherman und Mitarbeiter beschreiben in ihrer Zuschrift auf S. 16330 ff. die gezielte Entwicklung und Synthese eines photoresponsiven Makrocyclus, der bemerkenswerte Bindungsaffinitäten für einen Satz von Gastmolekülen, einschließlich N‐Oxiden und Carboxylaten, zeigt. Durch Bestrahlen des Komplexes mit UV‐Licht werden die Gastmoleküle aus der makrocyclischen Kavität freigesetzt. [ABSTRACT FROM AUTHOR]

The approach relies on a two-step condensation-reduction procedure, and the stereochemical outcome is reversed by the appropriate reducing agent. [ABSTRACT FROM AUTHOR]